Application Of Light-responsive DNA Nanoprobes In Tumor Signal Amplification Imaging

Early and accurate detection of cancer is essential for the safety and health of patients.With the deepening of cancer research,some tumor markers have gradually entered the public eye,such as tumor-related RNA,specific tumor proteins,etc.Therefore,imaging detection of tumor markers helps people accurately diagnose cancer.RNA mainly includes micro RNA,messenger RNA,etc.It is a kind of genetic information carrier present in biological cells and some viruses and viruses^[1-3].It is a very conserved regulator in living organisms.It is mainly responsible for regulating the expression of transcriptional and post-transcriptional genes in human and other animal cells.Thus far,there are about 48,860 mature mi RNAs distributed in 271 organisms.Studies have shown that mi RNAs are involved in about 30%of gene regulation and nearly 99%of genetic pathways regulation.As the messenger of genetic material,m RNA can transmit genetic information from DNA to the ribosome,where it serves as a template for protein synthesis and determines the amino acid sequence of the protein peptide chain of the gene expression product.Therefore,RNA plays a key role in cell development,proliferation,differentiation,apoptosis and other biological processes.Their disorders are related to the occurrence of numerous human diseases,including cancer,which means that they can be detected as tumor markers and play a vital role in the early diagnosis of cancer.Deoxyribonucleic acid（DNA）is considered one of the best materials for building nanomachines due to its excellent sequence specificity,favorable physical and chemical properties,and programmable supramolecular self-assembly.With these special properties,functions such as DNA signal amplification and fluorescence recovery imaging have been developed one after another.Therefore,in the field of biological imaging detection,DNA fluorescent probes are more and more widely used.However,nanomachines constructed only from DNA commonly encounter various difficulties in vivo applications due to their poor cell permeability and easy degradation.Therefore,the construction of an exogenous controllable DNA nano-probe delivery system is expected to become the key to early cancer monitoring and imaging.Around this problem,this paper innovatively designed two near-infrared light-controlled DNA nano-probe delivery systems.The main research content is as follows:1.Based on the thermal liposome-DNA nano-probe system,a light-controllable release DNA nano-probe that can be used for human breast cancer imaging is prepared.The system can specifically respond to TK1 m RNA in tumor cells and perform signal amplification imaging.First,the fluorescent agent,quencher-modified DNA double-strand and fuel chain are encapsulated in the thermal liposome,and the photothermal reagent ICG that can be used for continuous imaging guidance is introduced to obtain a thermal liposome-wrapped DNA nano-probe system,and the MUC1 aptamer is modified on the surface of the liposome to give it the targeting ability.After it is injected intravenously,the load distribution of the drug in the body is detected by ICG fluorescence.When it is observed that the drug reaches its maximum enrichment at the tumor site,ICG generates heat under 808 nm laser irradiation,causing the heat-sensitive liposome to rupture,thereby releasing the DNA probe and completing fluorescence recovery imaging in response to TK1mRNA.2.An entropy-driven DNA probe is combined with an auxiliary DNA fuel on hollow copper sulfide nano-particles（HCuSNPs）for intracellular miRNA imaging.First,an organic molecule with a two-window imaging function will be modified at the end of the DNA machine,and it will be fixed to the copper sulfide nano-particles modified with the DNA auxiliary fuel chain.Copper sulfide nano-particles can quench the fluorescence of MY-1057 properly.The photothermal effect of HCu SNPs induced by NIR-II can effectively release the anchored auxiliary DNA fuel chain.The DNA machine is activated by the target mi RNA through base complementary pairing binding,and the DNA fuel released in response to NIR-II is powered by a chain replacement reaction,which is achieved by strong fluorescence recovery.In the absence of additional enzymes or fuels,reliable intracellular low-abundance mi RNA imaging between different cells is achieved.This entropy-driven DNA nanosystem provides a simple and powerful tool for intracellular miRNA analysis and related biomedical applications.